Free fatty acid-induced miR-181a-5p stimulates apoptosis by targeting XIAP and Bcl2 in hepatic cells

Ajay K. Yadav, Teja Naveen Sata, Daksh Verma, Amit K. Mishra, Amrendra K. Sah, Md Musa Hossain, Kishor Pant, Senthil K. Venugopal

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3 Scopus citations


Aims: Non-alcoholic fatty liver disease is one of the major health concerns in the World. The dietary free fatty acids (FFAs) affect the metabolic status of the hepatocytes by modulating cellular pathways. In this study, we showed that free fatty acids stimulate apoptosis by upregulating miR-181a-5p expression, which in turn targets XIAP and Bcl2. Methods: Huh7 cells were incubated with FFAs for 72 h and the expression of XIAP, Bcl2, bax, pAkt, Akt, PTEN and β-actin were determined by Western blots, and miR-181a-5p expression was determined using real-time RT-PCR. The Huh7 cells were transfected with either miR-181a-5p pre-miRs or anti-miR-181a-5p and the regulation of apoptosis and proliferation was studied. Three groups of C57BL/6 mice (n = 6 per group) were fed with standard diet, CSAA or CDAA diet for 6, 18, 32 and 54 weeks. Total protein and RNA were isolated from the liver tissues and used for Western blots and real-time RT-PCR respectively. Key findings: FFAs inhibited Akt phosphorylation, expression of XIAP and Bcl2, while upregulating the expression of PTEN, bax, and miR-181a-5p in Huh7 cells. Similar results were observed when the Huh7 cells were transfected with miR-181a-5p premiRs, while these changes were reversed in anti-miR-181a-5p-transfected, FFA-treated Huh7 cells. The CDAA-fed mice showed a significant inhibition of Akt phosphorylation, XIAP and Bcl2, whereas PTEN and bax expression were upregulated. The expression of miR-181a-5p was also significantly higher in CDAA-fed mice. Significance: These findings showed that free fatty acids induced apoptosis via upregulating miR-181a-5p in hepatic cells.

Original languageEnglish (US)
Article number120625
JournalLife Sciences
StatePublished - Jul 15 2022

Bibliographical note

Funding Information:
The authors thank Mr. Nitin Sharma and Mr. Milind Dongerdive for the technical help provided. The authors thank the Department of Science and Technology, Government of India , for providing the research grant [ EMR/2015/001304 ] and the South Asian University, New Delhi, India, for providing the research fellowships.

Publisher Copyright:
© 2022 Elsevier Inc.


  • Apoptosis
  • Bcl2
  • CDAA
  • NASH
  • XIAP
  • microRNA-181a-5p

PubMed: MeSH publication types

  • Journal Article


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